Effect of an Individually Tailored and Home-Based Intervention in the Chronic Phase of Traumatic Brain Injury

Key Points Question Does a home-based intervention that is individually tailored and goal oriented improve health-related quality of life (HRQOL) and participation and ameliorate symptoms in the chronic phase of traumatic brain injury (TBI)? Findings In this randomized clinical trial including 120 adult participants in the chronic phase of TBI, no significant results were seen in disease-specific HRQOL or social participation. However, generic HRQOL and TBI- and anxiety-related symptom levels improved significantly in the intervention group compared with the control group. Meaning These findings suggest that an individually tailored and goal-oriented rehabilitation program might be effective in improving generic HRQOL and symptom burden in the chronic phase of TBI.

Traumatic brain injury (TBI) is a condition affecting the persons' central nervous system with a need for extensive and highly specialized initial health care provision followed by comprehensive rehabilitation efforts. Frequent and life-long medical, cognitive, emotional and behavioral changes are expected. The community-based services are largely responsible for dealing with the chronic challenges affecting people with TBI.

The main study purpose and hypotheses
The main study purpose is to examine the long-term treatment needs and the effect of a goal-oriented community-based rehabilitation program for individuals with TBI living at home, with the following main research hypotheses: • Person-centered intervention targeting the patients living environment will result in enhance goal achievement in participation and in lower burden of self-reported TBI related problems compared to the control group at the end of intervention, and 8 months after intervention (i.e., at 12 month after enrolling) • Person-centered intervention will result in improved physical and mental health compared to the control group, at the end of intervention and 12 month follow-up. • Person-centered intervention will result in fewer unmet health care needs compared to the control group, at the end of intervention and 12 month follow-up. • Person-centered intervention will be a cost-effective alternative compared to the treatment as usual received by the control group. • Patients, family members and rehabilitation professionals involved will be satisfied with the intervention program

Study design
Two-group RCT design.

Setting
In-home community based rehabilitation in the chronic phase of TBI (2-5 years post injury), in close collaboration with family members and local rehabilitation professionals. Patients are excluded if they have severe preexisting neurological disorder or severe psychiatric diseases that would confound outcome assessments.

Recruitment and randomization
Eligible patients who consent to participation will be randomly allocated to either the intervention group or the control group in a 1:1 ratio. Internet-based block randomization with minimization will be used to ensure randomization and complete allocation concealment. Potential prognostic variables such as age, gender and injury severity will be balanced between groups. An investigator who is independent of the patient screening process will be responsible for allocating the patients to the study conditions. Blinding of the patients and rehabilitation professionals is not possible in this study, but the outcome assessors will be blinded to study group.

Group allocation and interventions
1. Pilot study: To help set-up the intervention programs and determine feasibility of the interventions, the recruitment process (participation, refusals) and the implementation of procedures and necessary adjustment regarding content and number of sessions, a pilot study involving 10 patients with their close family members (10% of total number) will be performed prior to the full scale RCT. This pilot will also explore compliance from the patients, family members and local health professions, feasibly registrations of compliance as well as the time consumption and acceptability of the intervention.

2.
The patient-centered in-home program intervention will be modeled with reference to the Winter et al. study (1), which consists of eight contacts (six in-home visits of 1-2 hours duration each and two telephone contacts), delivered over a 4-month period in three phases: Phase I: assessment of patients' needs and main activity limitations (target outcomes) in collaboration with the patient, family member and patient family doctor or responsible local rehabilitation health care professional, along with review of the purpose of intervention. Phase II: Defining specific goals and action planning based on the SMART goals model, where SMART goals need to be Specific, Measurable, Achievable, Realistic, and Timed (2). This ensures an individual goal setting plan documenting targeted activities and strategies for each identified problem in multi-level domains of functioning (contacts 1-3); Phase III: establishment of strategies to modify the physical and psycho-social environment and of compensatory strategies and training to deal with targeted symptoms, included a final in-home visit (contact 3-8).

Establishment of functional target outcome areas and SMART-goals
Identifying target outcome areas as experienced by both the patients and their relatives, is done by asking them to list the most and the next most troubling symptom due to their brain injury, as well as indicate on a 5-point Likert scale how difficult these problems are to deal with (from 0=not at all, to 4=extremely).
Up to three target outcomes will be identified. The Likert scale evaluation of the target outcomes will also be used as an outcome measure. There might be marked discrepancies in patients´ and relatives' subjective experience of symptoms and how troubling they are. Therefore, specific SMART goals will be established (2), based on the target outcomes, where both the perspective of the patient and the family member will be taken into account. Goals will be ensured to address functional domains in every day living. There might thus be more than one specific goal connected to each target outcome area. Goal attainment will be measured at outcome using Goal Attainment Scaling (GAS) (3). Goals are classified according to their importance, on a scale of 0-3 ranging from 0="not at all" to 3="very" important. Goal attainment is classified as being between +2 and -2, where a score of 0 represents goal attainment at the expected level pre-treatment, -1 and -2 correspond to a little and a lot worse goal attainment than expected, respectively, and likewise, +1 and +2 represent goal attainment that is a little more or a lot more than anticipated.
This represents a highly structured way of establishing the functional areas that patients and relatives want to address, along with establishment of specific treatment goals, and ensures that the treatment relates to personally relevant problem areas. The Likert scale evaluation of severity of target outcomes, along with scoring of goal importance and goal attainment, additionally ensures that a patient-centered perspective can be combined with quantifiable outcomes that are comparable across participants.

Intervention content
Based on well-established knowledge about the most common long-term symptoms after moderate to severe TBI, and the experiences of Winter et al (1;4;5), we expect that target outcomes and related goals will predominantly be related to cognitive (e.g. memory, attention, executive functioning & selfawareness, communication), physical (e.g. sensory and motor deficit, fatigue, dizziness, reduced balance, visual problems), emotional (e.g. anxiety and depression secondary to injury, stress management), and interpersonal problems (e.g. reduced awareness of deficit, personality changes, disinhibited behavior, apathy, irritability).
In addition to providing a structured treatment program, one main goal of this study is for the specialist health care system to contribute to community-based rehabilitation being in accord with evidence based practice. In order to ensure high quality interventions, the study will therefore include components from evidence-based treatment programs within relevant functional domains, enabling adaptation of specialized rehabilitation programs to the home-setting. Interventions addressing cognition will be in accord with state-of-the art reviews of cognitive rehabilitation (6). The Translating Evidence-Based Recommendations into Practice document will also inform intervention content. Choice of interventions will adhere to the recommended decision trees in aforementioned reviews. As the current study involves TBI with intracranial injuries revealed at the neuroimaging in the acute phase, while Winter and colleagues predominantly treated mild injuries, symptom severity is expected to be of more severe grade. An important principle within TBI rehabilitation is to start out with establishing symptom severity, along with the patients´ symptom awareness, and consequently, motivation for rehabilitation efforts targeting that specific domain. In general, the more severe the symptoms are, the more the interventions need to involve environmental modifications. On the other hand, in cases of mild to moderate symptom burden, and good symptom awareness, the interventions can to a larger degree be based on training of internal compensatory strategies and metacognitive strategies. Systematic use of compensatory devices and external aids will be part of the intervention tool-box.
Muscle relaxation and mindfulness techniques will be used to address problems with stress management. Regarding symptoms of anxiety and depression, techniques derived from Cognitive Behavioral Therapy will be the dominating theoretical approach, although an eclectic stance will be taken, e.g. in cases where threats to identity and self-concept are seen to be more readily addressed using other therapeutic approaches (7).
Based on the identified target outcomes and the corresponding SMART-goals, an action plan will be established for each patient, in accord with Winter et al. In the action plan, the specific interventions chosen in relation to each goal will be described. The flow-chart below describes the process of establishing a specified and patient-centered intervention strategy with corresponding measurable outcomes.
Received services during the study period will be registered by the Needs and provision complexity scale part B.

TARGET OUTCOMES
A) Establish up to three target outcomes. B) Rate each outcome regarding how difficult the symptom is to deal with (from 0 to 4)

SMART-GOALS
A) Establish distinct SMART-goals within each target outcome B) Define distinct intervention to be applied in relation to each goal

ACTION PLAN
Establish action plan which includes target outcome areas, corresponding goals and specified intervention strategy pertaining to each SMART-goal Procedurecollaboration with the local health care professionals and intervention delivery: the patient will nominate his/her primary local health care professional to join the intervention sessions. For participants who are not connected to a local health care professional, the study investigators will establish such a contact in collaboration with the patient´s general medical doctor. The involvement of the municipal health care professional in the intervention will ensure lasting knowledge transference. The principal investigator in collaboration with senior TBI researchers will supervise the study interventionists (trained allied neurorehabilitation professionals). Concerns about the protocols will be discussed and resolved in project meetings throughout the project period.
3. The control group will receive the usual follow-up assessment and health care and rehabilitation services provided in the municipality. At the time of inclusion, patients in the control group will selfidentify their main problems and rehabilitation goals for the next 4-6 months. The received services will be registered and mapped according to the ICSO-R over the study period. The control group will be followed-up by two attention-telephone calls to maintain contact with participants and to registered any changes that might have occurred and reminders about the follow-up interviews

Data collection
Baseline assessment of cognitive, emotional, functional and participation status will be performed at inclusion (= T1), with outcome assessments being performed immediately following the intervention (= T2) and 8 months after end of the intervention (= T3).
The assessments will be performed at the outpatient clinic of Department of Physical Medicine and Rehabilitation,Oslo University Hospital.

Patient characteristics
The following socio-demographic variables will be recorded at baseline: age, gender, marital status, living conditions, educational level and description of pre-injury employment. Medical variables including comorbidity, injury characteristics and clinical severity (Glasgow Coma Scale Score, Posttraumatic amnesia), neuroimaging results, length of acute and inpatients hospitalizations, medical and rehabilitation treatment modalities during the first year after the injury will be derived from the medical journal. In addition, the data regarding participation in paid employment or education and the use of health care and rehabilitation services beyond the first year of injury will be collected. Assessment of patients' needs for health care and social support services by patient, family member and clinician will also be collected at the study inclusion time, along with a neuropsychological screening of IQ, memory, processing speed and executive functioning (Vocabulary, Similarities, Block design and Matrix Reasoning from the Wechsler Adult Intelligence Scale (WAIS-IV), California Verbal Learning Test-II, the Processing Index from the Wechsler Adult Intelligence Scale-IV, the Trail Making and Color Word Interference Tests from the

Outcome assessment
Severity of target outcomes, goal attainment, participation in the community and met health care needs are the main areas targeted, and will be focused in the assessments and outcome evaluations along with cognitive, emotional and global functioning measures, and satisfaction with services (Table 1) The participation rate, numbers of consultations, the direct and indirect time related to each consultation, the kind of problems presented, completion of intervention due to protocol and in case of noncompliance, reason for non-compliance. After completion of the intervention, the participants and family members will be asked to evaluate the intervention (9) and how satisfied they are with the intervention.

Determination of costs
Data concerning cost will be gathered prospectively using monthly cost-diaries. All participants will be asked to note all their health care utilizations during that month. For the calculation of total costs, direct health care costs, direct non-health costs and indirect costs will be recorded such as visits to health care providers and medication costs, the costs of informal health care, cost of health activities, hours of paid or unpaid household help and special aids as well as loss of paid and unpaid work productivity of the patient.
Costs of interventions will also be calculated.

Analysis and statistics
All data will be anonymously coded and registered electronically in SPSS. T-test analysis will be used for between-group mean comparisons for normally distributed continuous data, and Mann Whitney U-tests for skewed data. Regression analysis will be applied using the main variables of interest to predict outcomes. In order to test whether the intervention has a beneficial effect on goal attainment, participation symptom level and functioning, compared to the control group, mixed model analysis will be used with time (T1-T3) as the repeated-measures factor, and comparison between the intervention and control groups being a between group factor. Intention to treat analyses will be performed adjusted for sociodemographic and service content variables from ICSO-R. To evaluate the effect of the intervention, 50 patients need to be completing the intervention in each group, based on the experiences from Winter et al (1), which required power of 90% and a significance level of 0,05. With an estimated loss to follow-up of 20%, based on our earlier TBI research, 120 participants are thought to be necessary and sufficient for this trial. Intention to treat analyses will be performed for the randomized trial. The descriptive approach will be used for analyses of process evaluation.
To determine the cost-effectiveness of the intervention, a statistical analysis of costs will be performed. The total costs will be calculated by adding up direct health care costs, direct non-health costs and indirect costs. As the distribution of costs can be skewed, differences in costs between groups will be calculated by means of bootstrapping. A cost-utility analysis will relate the difference between the intervention and control group to changes in utility. This will result in costs per quality-adjusted-life years (QALYs). QALYs can be derived from the SF-36 data using SF-6D (10) Standard discounting will be performed for both costs and outcomes together with sensitivity and uncertainty analysis to gain insight into the generalizability of the economic evaluation.